6paf
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Co-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors== | |
| + | <StructureSection load='6paf' size='340' side='right'caption='[[6paf]], [[Resolution|resolution]] 1.24Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6paf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PAF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PAF FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=O6A:N-(1-{[4-(aminomethyl)phenyl]sulfonyl}piperidin-4-yl)-5-cyclopropyl-1,2-oxazole-3-carboxamide'>O6A</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6p6k|6p6k]], [[6p6g|6p6g]], [[6p7z|6p7z]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SMYD3, ZMYND1, ZNFN3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6paf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6paf OCA], [http://pdbe.org/6paf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6paf RCSB], [http://www.ebi.ac.uk/pdbsum/6paf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6paf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/SMYD3_HUMAN SMYD3_HUMAN]] Histone methyltransferase. Specifically methylates 'Lys-4' and 'Lys-5' of histone H3, inducing di- and tri-methylation, but not monomethylation. Plays an important role in transcriptional activation as a member of an RNA polymerase complex. Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences.<ref>PMID:15235609</ref> <ref>PMID:22419068</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report herein the discovery of isoxazole amides as potent and selective SET and MYND Domain-Containing Protein 3 (SMYD3) inhibitors. Elucidation of the structure-activity relationship of the high-throughput screening (HTS) lead compound 1 provided potent and selective SMYD3 inhibitors. The SAR optimization, cocrystal structures of small molecules with SMYD3, and mode of inhibition (MOI) characterization of compounds are described. The synthesis and biological and pharmacokinetic profiles of compounds are also presented. | ||
| - | + | Discovery of Isoxazole Amides as Potent and Selective SMYD3 Inhibitors.,Su DS, Qu J, Schulz M, Blackledge CW, Yu H, Zeng J, Burgess J, Reif A, Stern M, Nagarajan R, Pappalardi MB, Wong K, Graves AP, Bonnette W, Wang L, Elkins P, Knapp-Reed B, Carson JD, McHugh C, Mohammad H, Kruger R, Luengo J, Heerding DA, Creasy CL ACS Med Chem Lett. 2019 Dec 27;11(2):133-140. doi:, 10.1021/acsmedchemlett.9b00493. eCollection 2020 Feb 13. PMID:32071679<ref>PMID:32071679</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Elkins, P | + | <div class="pdbe-citations 6paf" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Histone-lysine N-methyltransferase]] | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Elkins, P A]] | ||
[[Category: Wang, L]] | [[Category: Wang, L]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Methyltransferase]] | ||
| + | [[Category: Oncology]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 07:58, 11 March 2020
Co-crystal Structure of human SMYD3 with Isoxazole Amides Inhibitors
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